title: Ceramides: a potential therapeutic target in pulmonary emphysema.
abstract: BACKGROUND
  The aim of this manuscript was to characterize airway ceramide profiles in a rodent model of elastase-induced emphysema and to examine the effect of pharmacological intervention directed towards ceramide metabolism.
  
  
  METHODS
  Adult mice were anesthetized and treated with an intratracheal instillation of elastase. Lung function was measured, broncho-alveolar lavage fluid collected and histological and morphometrical analysis of lung tissue performed within 3 weeks after elastase injection, with and without sphingomyelinase inhibitors or serine palmitoyltransferase inhibitor. Ceramides in broncho-alveolar lavage (BAL) fluid were quantified by tandem mass spectrometry.
  
  
  RESULTS
  BAL fluid showed a transient increase in total protein and IgM, and activated macrophages and neutrophils. Ceramides were transiently upregulated at day 2 after elastase treatment. Histology showed persistent patchy alveolar destruction at day 2 after elastase installation. Acid and neutral sphingomyelinase inhibitors had no effect on BAL ceramide levels, lung function or histology. Addition of a serine palmitoyltransferase inhibitor ameliorated lung function changes and reduced ceramides in BAL.
  
  
  CONCLUSIONS
  Ceramides were increased during the acute inflammatory phase of elastase-induced lung injury. Since addition of a serine palmitoyltransferase inhibitor diminished the rise in ceramides and ameliorated lung function, ceramides likely contributed to the early phase of alveolar destruction and are a potential therapeutic target in the elastase model of lung emphysema.
authors.affiliation: Physiology and Experimental Medicine Program, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. martin.post@sickkids.ca.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Tibboel
authors.forename: Irwin
authors.initials: I
authors.lastname: Reiss
authors.forename: Johan C
authors.initials: JC
authors.lastname: de Jongste
authors.forename: Martin
authors.initials: M
authors.lastname: Post
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002518:Ceramides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase / Q000009:adverse effects; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D051102:Serine C-Palmitoyltransferase / Q000037:antagonists & inhibitors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002518:Ceramides; D004791:Enzyme Inhibitors; D051102:Serine C-Palmitoyltransferase; D010196:Pancreatic Elastase